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The aromatic structure of three different-rank vitrinites, V-YJL (Ro =0.61%), V-AW (Ro =1.13%), and V-JC (Ro =2.22%), was investigated by X-ray diffraction (XRD), high-resolution transmission elect...

A series of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives (10a–10x) were designed, synthesized, and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against the SH-SY5Y, MDA-MB-231, A549, and HepG2 cell lines. Most of the compounds remarkably inhibited c-Met kinase and showed moderate to good cytotoxicity and selectivity toward the four cancer cell lines. Among them, compounds 10b and 10f were the two most potent selective c-Met inhibitors with half-maximal inhibitory concentration (IC50) values of 5.17 ± 0.48 nM and 5.62 ± 0.78 nM, respectively, and suppression abilities comparable with the positive control cabozantinib. Cell proliferation assay further demonstrated that the two most promising compounds 10a and 10b also showed good cytotoxicity and selectivity toward MDA-MB-231 cells, with IC50 values of 26.67 ± 2.56 μM and 26.83 ± 2.41 μM, respectively. Compounds 10f and 10g showed cytotoxicity and selectivity toward A549 cells, with IC50 values of 20.20 ± 2.04 μM and 21.65 ± 1.58 μM, respectively. All antiproliferative activities were within the range of those of cabozantinib. Notably, these compounds presented relatively low hepatotoxicity compared with reference drugs. Moreover, the preliminary structure–activity relationship and docking studies revealed that replacement of a nitrogen-containing heterocycle on the R2 (block A) group might improve the c-Met kinase inhibitory and antiproliferative effects in MDA-MB-231 cells, whereas displacement by a substituted benzene ring, especially for the p-fluorophenyl or 4-fluoro-3-methoxyphenyl moiety, on the R2 group enhanced cytotoxicity toward A549 cells. Together, these results suggest that 10b and 10f are promising compounds and provide a basis for their development as new antitumor agents.

Tyrosinase plays a key role in the melanin biosynthesis since it catalyzes the transformation of tyrosine into L-dopaquinone. A large number of studies have also shown that molecules to efficiently inhibit the activity of tyrosinase would be potentially used in treating many depigmentation-related disorders. In this study, we targeted a series of structure-based 3-aryl substituted xanthone derivatives in which diverse functional groups were respectively attached on 3-aromatic ring moiety as new tyrosinase inhibitors. The results demonstrated that all obtained compounds had potent tyrosinase inhibitory activities with IC50 values at micromolar range. Especially, compound 4t was found to be the most active tyrosinase inhibitor with the IC50 value of 11.3 µM, uncovering that the introduction of the proper hydroxyl group in the 3-aromatic ring was beneficial for enhancing the inhibitory potency against tyrosinase. Moreover, the inhibition mechanism and inhibition kinetics studies revealed that compound 4t presented such inhibitory effect by acting as the reversible and competitive-uncompetitive mixed-II type inhibitor. Further molecular docking simulation showed that 3-aromatic ring of compound 4t was inserted into the narrow regions of binuclear copper-binding site at the bottom of the enzyme binding pocket, while the xanthone skeleton was positioned at the surface of tyrosinase. Taken together, these data suggested that such type of molecules might be utilized for the development of new and promising candidate for the treatment of depigmentation-related disorders.

A series of novel ligustrazine derivatives 8a&ndash, r were designed, synthesized, and evaluated as multi-targeted inhibitors for anti-Alzheimer&rsquo, s disease (AD) drug discovery. The results showed that most of them exhibited a potent ability to inhibit both ChEs, with a high selectivity towards AChE. In particular, compounds 8q and 8r had the greatest inhibitory abilities for AChE, with IC50 values of 1.39 and 0.25 nM, respectively, and the highest selectivity towards AChE (for 8q, IC50 BuChE/IC50 AChE = 2.91 &times, 106, for 8r, IC50 BuChE/IC50 AChE = 1.32 &times, 107). Of note, 8q and 8r also presented potent inhibitory activities against A&beta, aggregation, with IC50 values of 17.36 &micro, M and 49.14 &micro, M, respectively. Further cellular experiments demonstrated that the potent compounds 8q and 8r had no obvious cytotoxicity in either HepG2 cells or SH-SY5Y cells, even at a high concentration of 500 &mu, M. Besides, a combined Lineweaver-Burk plot and molecular docking study revealed that these compounds might act as mixed-type inhibitors to exhibit such effects via selectively targeting both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChEs. Taken together, these results suggested that further development of these compounds should be of great interest.

It is a challenge for the distribution grid with more and more PV generation connected. The limit capacity calculation of PV generation is the key for the problems of distribution grid. The paper proposes method for the calculation of limit capacity of PV generation in the distribution grid. The proposed model takes the maximum capacity of PV generation as the objective, and the operation constraints contain bus voltage deviation, line current, main transformer limit, reactive power compensation and power turning. Fish swarm algorithm is used for the calculation of the limit capacity of PV generation. The simulation of IEEE33 bus system shows that the proposed method can increase the grid-connected limit capacity of PV generation under the premise of meeting the constraints of distribution grid system. It verifies the rationality and feasibility of the proposed method, and provides a solution for the limit capacity of distributed PV generation connected into distribution grid.

Enhancing the light absorption in ultrathin-film silicon solar cells is important for improving efficiency and reducing cost. In this paper, we report a highly effecient cosine periodic nanostructure as light trapping texture. The design and fabrication as well as measurement of cosine nanotextures were presented. The optimized structure yields an average reflectance of 7.07% at an equivalent silicon thickness of 10μm, much better than planar and random pyramid structures. The measurements demonstrate that the absorptions in ultrathin film solar cells are very close to the Yablonovitch limit for the entire solar spectrum and insensitive to the angle of the light. This approach is applicable to various thicknesses and promising in future glass-based thin film solar cells.